title: Association of complement 5 genetic polymorphism with renal allograft outcomes in Korea.
abstract: BACKGROUND
  Complements play important roles in both rejection and ischemia-reperfusion injury after transplantation. Complement 5 (C5) is a pivotal complement, which initiates the assembly of the membrane attack complex, and mediates chemotaxis of various immune cells. We investigated the impacts of genetic variations in C5 and its receptor (C5aR) of both recipients and donors on renal allograft outcomes.
  
  
  METHODS
  Seven single-nucleotide polymorphisms (SNPs) in C5 (rs12237774, rs2159776, rs17611, rs25681, rs2241004, rs10985126 and rs10818500) and one SNP (rs10404456) in the C5aR gene were genotyped in 191 recipient-donor pairs. The association of the polymorphisms with allograft outcomes was determined.
  
  
  RESULTS
  Three C5 SNPs (rs2159776, rs17611 and rs25681) in recipients had a tendency toward a reduced glomerular filtration rate at 1 year after transplantation. There were four haplotypes in the H2 linkage disequilibrium block, which was formed by four SNPs (rs2159776, rs17611, rs25681 and rs2241004). The GGCG haplotype in both recipients and donors was associated with lower glomerular filtration rate at 1 year (60.9 ± 15.9 versus 66.4 ± 15.5 mL/min/1.73 m(2), P = 0.020; 60.6 ± 15.3 versus 66.2 ± 15.8 mL/min/1.73 m(2), P = 0.017). The association was sustained over 7 years after transplantation (P = 0.015 in recipients; P = 0.039 in donors). The presence of the GGCG haplotype in recipients was associated with poorer graft survival (logrank test, P = 0.024). However, C5 polymorphisms were not correlated with serum C5 level. C5aR polymorphism had no significant impact on the allograft outcomes.
  
  
  CONCLUSIONS
  The GGCG haplotype of C5 in both recipients and donors was associated with lower renal allograft function.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. jcyjs@dreamwiz.com
authors.forename: Jong Cheol
authors.initials: JC
authors.lastname: Jeong
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Hwang
authors.forename: Hyosang
authors.initials: H
authors.lastname: Kim
authors.forename: Han
authors.initials: H
authors.lastname: Ro
authors.forename: Hayne Cho
authors.initials: HC
authors.lastname: Park
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Myung-Gyu
authors.initials: MG
authors.lastname: Kim
authors.forename: Jongwon
authors.initials: J
authors.lastname: Ha
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Dong Wan
authors.initials: DW
authors.lastname: Chae
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
authors.forename: Jaeseok
authors.initials: J
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D003182:Complement C5 / Q000235:genetics*; D005260:Female; D005838:Genotype; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000628:therapy; D016030:Kidney Transplantation; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics; D056910:Republic of Korea; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D003182:Complement C5; D044087:Receptor, Anaphylatoxin C5a